Takahashi M, Taniguchi T, Murata S, Okada K, Moriyama N, Yamazaki S, Muramatsu I
Department of Pharmacology, School of Medicine, Fukui Medical University, Matsuoka, Japan.
J Urol. 1999 Apr;161(4):1350-4.
We compared the affinities of a new alpha1-adrenoceptor (AR) antagonist, JTH-601 with those of several alpha1-AR antagonists in human prostates and arteries.
In the functional study, noradrenaline produced concentration-dependent contractions in human prostates and mesenteric arteries. The pA2/pKB values for the antagonists in the human prostate were 9.78 for tamsulosin, 8.84 for JTH-601, 8.39 for WB4101, 8.23 for prazosin, 8.12 for JTH-601-G1 (a main metabolite of JTH-601 in human) and 6.57 for BMY7378. Compared these affinities with those in the mesenteric artery, only JTH-601 and JTH-601-G1 exhibited unique uroselectivity, showing 10- to 20-fold higher affinity for the human prostate than for mesenteric artery. The affinity profile of these antagonists suggested that the noradrenaline-induced contractions in the human prostate and the mesenteric artery were mediated by the alpha1L-AR and alpha1B-AR, respectively. In the competition binding study, the pharmacological profiles of the antagonists against [3H]-prazosin were examined in the human prostate and aorta. The resulting pKi values for JTH-601 and JTH-601-G1 were also approximately 10- to 20-fold higher for the human prostate than for the human aorta.
These results have suggested that JTH-601 and JTH-601-G1 are unique uroselective alpha1-AR antagonists that show higher affinity for the human prostate than for the human arteries.
我们比较了新型α1肾上腺素能受体（AR）拮抗剂JTH - 601与几种α1 - AR拮抗剂在人前列腺和动脉中的亲和力。
在功能研究中，去甲肾上腺素在人前列腺和肠系膜动脉中产生浓度依赖性收缩。在人前列腺中，拮抗剂的pA2/pKB值分别为：坦索罗辛9.78、JTH - 601 8.84、WB4101 8.39、哌唑嗪8.23、JTH - 601 - G1（JTH - 601在人体内的主要代谢产物）8.12、BMY7378 6.57。将这些亲和力与肠系膜动脉中的进行比较，只有JTH - 601和JTH - 601 - G1表现出独特的尿选择性，对人前列腺的亲和力比对肠系膜动脉高10至20倍。这些拮抗剂的亲和力谱表明，去甲肾上腺素在人前列腺和肠系膜动脉中诱导的收缩分别由α1L - AR和α1B - AR介导。在竞争结合研究中，在人前列腺和主动脉中检测了拮抗剂对[3H] - 哌唑嗪的药理学谱。JTH - 601和JTH - 601 - G1在人前列腺中的所得pKi值也比对人主动脉高约10至20倍。
这些结果表明，JTH - 601和JTH - 601 - G1是独特的尿选择性α1 - AR拮抗剂，对人前列腺的亲和力高于对人动脉的亲和力。
